Current issues of ACP Journal Club are published in Annals of Internal Medicine


Review: Several pharmacologic therapies promote modest weight loss


ACP J Club. 2005 Sep-Oct;143:50. doi:10.7326/ACPJC-2005-143-2-050

Related Content in this Issue
• Companion Abstract and Commentary: Review: Sparse high-quality evidence supports surgery for obesity

Clinical Impact Ratings

GIM/FP/GP: 5 stars

Endocrinology: 5 stars

Source Citation

Li Z, Maglione M, Tu W, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med. 2005;142:532-46. [PubMed ID: 15809465]



How effective and safe are pharmacologic therapies in the treatment of obesity?


Data sources: MEDLINE (to July 2003), the Cochrane Central Register of Controlled Trials, and existing systematic reviews.

Study selection and assessment: Randomized controlled trials that evaluated pharmaceutical agents for weight loss in patients with body mass index ≥ 27 kg/m2 and reported ≥ 6-month weight outcomes. Study quality was assessed using the 5-point Jadad scale (5 = highest quality) and considered study design, method of random assignment, blinding, and withdrawal.

Outcomes: Weight loss and side effects.

Main results

The studies meeting inclusion criteria were 3 existing meta-analyses (39 RCTs) evaluating sibutramine, phentermine, and diethylpropion, and 47 RCTs that evaluated orlistat, bupropion, topiramate, and fluoxetine. All comparisons were with placebo, and most trials had a hypocaloric diet co-intervention. Meta-analyses were done using random effects. Most medications led to modest weight loss compared with placebo; side effects varied by drug (Table).


On average, sibutramine, phentermine, orlistat, diethylpropion, bupropion, topiramate, and fluoxetine led to 1 to 7 kg of weight loss by 6 months in obese adults with body mass index ≥ 27 kg/m2.

Source of funding: Agency for Healthcare Quality and Research.

For correspondence: Dr. Z. Li, West LA Veterans Affairs Medical Center, Los Angeles, CA, USA. E-mail

Table. Medical therapies vs placebo for obesity*

Drug Number of placebo-controlled RCTs Follow-up Weight loss (kg) (95% CI or range) Commonly reported side effects
Sibutramine 12 16 to 24 wk −3.4 to −6.0 Increased heart rate (4 beats/min)
5 44 to 54 wk −4.5 (−5.3 to −3.6)
Phentermine 6 2 to 24 wk −3.6 (−6.0 to −0.6) Palpitations, tachycardia, increased blood pressure, central nervous system and gastrointestinal effects
Diethylpropion 9 6 to 52 wk −3.0 (−11.5 to 1.6) Central nervous system effects, dizziness, headache, insomnia, restlessness, increased blood pressure, palpitations, tachycardia, gastrointestinal effects, rash
Orlistat 12 6 mo −2.6 (−3.5 to −1.7) Diarrhea, flatulence, bloating, abdominal pain, dyspepsia
22 12 mo −2.9 (−3.5 to −2.3)
Fluoxetine 7 6 mo −0.9 to −9.1 Nervousness, sweating, tremors, nausea, vomiting, fatigue, asthenia, hypersomnia, somnolence, insomnia, diarrhea
6 12 mo −14.5 to 0.4
Bupropion 3 6 to 12 mo −2.8 (−4.5 to −1.1) Dry mouth
Topiramate (percentage weight loss) 6 6 mo −6.5% (−8.3 to −4.8) Paresthesia, taste perversion, central nervous system effects, constipation, dry mouth, upper abdominal symptoms, fatigue

*RCT = randomized controlled trial; CI defined in Glossary. A random-effects model was used.


Obesity is a chronic condition resulting from a myriad of factors causing an imbalance of energy intake and expenditure. Although lifestyle changes can result in weight loss for some, many obese patients need more efficacious interventions for weight reduction. The use of pharmacologic and surgical treatments has increased in response to the increasing prevalence of obesity.

Li and colleagues and a Cochrane review on this topic (1) agree that several available medications combined with dietary intervention result in average weight loss of about 3 to 5 kg in excess of placebo with relatively mild short-term side effects.

Although a 5% to 10% weight loss can result in reduced risk for chronic disease (2), Foster and colleagues showed that most patients achieving the degree of weight loss reported with pharmacotherapy by Li and colleagues would be “very disappointed” (3). A group underrepresented in pharmacologic trials, severely obese patients (BMI > 40 kg/m2), may perceive less palliation from a “modest” weight loss. Large loss to follow-up in trials and in clinical practice may, in part, reflect limitations of medical therapy and complicate the interpretation of trials.

With this in mind, clinicians should appreciate why some patients are enamored with surgical treatments for obesity. Maggard and colleagues noted that although current high-quality data are lacking, a large observational study from Sweden supports the efficacy and probable superiority of surgical treatments for severely obese patients. When considering the large, consistent differences in weight, major comorbid outcomes observed, and low risk for major complications in a large number of patients, they suggest it is more likely that the differences are attributable to surgical treatment and not due to unmeasured variables. Consistent findings from other investigators have been published (4). Still, RCTs are needed to establish causality and to detect small differences (particularly between surgical procedures) in outcomes important to patients, including quality of life and cost-effectiveness.

Clinicians should consider many variables before generalizing these data to patient care, as they may not reflect such variables as advancements in surgical techniques, differences in technical skill, refined systems of care (e.g., multidisciplinary bariatric surgery teams), patient age, and the addition of co-interventions (e.g., behavior therapy and support groups). Further research needs to explore the largely unexplained differences in results among many of the weight loss therapy trials. These differences suggest that patient populations with specific barriers to effective weight loss or specific comorbid conditions may respond better to different types of weight loss drugs, combinations of drugs, and co-interventions.

Clinicians should work with patients to define important outcomes, including the magnitude of weight loss, effect on relevant obesity-related cormorbid conditions, and cost to identify patients' tolerance of risk for adverse events and to convey the uncertainty about the available evidence.

Kurt A. Kennel, MD
Mayo Clinic
Rochester, Minnesota, USA


1. Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for obesity and overweight. Cochrane Database Syst Rev. 2004;(3):CD004094. [PubMed ID: 15266516]

2. Goldstein DJ. Beneficial health effects of modest weight loss. Int J Obes Relat Metab Disord. 1992;16:397-415. [PubMed ID: 1322866]

3. Foster GD, Wadden TA, Phelan S, Sarwer DB, Sanderson RS. Obese patients' perceptions of treatment outcomes and the factors that influence them. Arch Intern Med. 2001;161:2133-9. [PubMed ID: 11570944]

4. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292:1724-37. [PubMed ID: 15479938]